BackgroundTakayasu’s arteritis (TA) is a chronic inflammatory disease affecting the large arteries and their branches; its etiology is still unknown. In individuals suffering from TA, arterial inflammation progresses to stenosis and/or occlusion, leading to organ damage and affecting survival. Relation of TA with Mycobacterium tuberculosis has been known, but there have been only a few systematic studies focusing on this association. The IS6110 sequence identifies the Mycobacterium tuberculosis complex and the HupB establishes the differences between M. tuberculosis and M. bovis. Our objective was to search the presence of IS6110 and HupB genes in aorta of patients with TA.MethodsWe analyzed aorta tissues embedded in paraffin from 5760 autopsies obtained from our institution, we divided the selected samples as cases and controls; Cases: aortic tissues of individuals with Takayasu’s arteritis. Control positive: aortic tissues (with tuberculosis disease confirmed) and control negative with other disease aortic (atherosclerosis).ResultsOf 181 selected aorta tissues, 119 fulfilled the corresponding criteria for TA, TB or atherosclerosis. Thus 33 corresponded to TA, 33 to tuberculosis (TB) and 53 to atherosclerosis. The mean age was 22 ± 13, 41 ± 19, and 57 ± 10, respectively. IS6110 and HupB sequences were detected in 70% of TA tissues, 82% in tuberculosis, and in 32% with atherosclerosis. Important statistical differences between groups with TA, tuberculosis versus atherosclerosis (p = 0.004 and 0.0001, respectively) were found.ConclusionWe identified a higher frequency of IS6110 and HupB genes in aortic tissues of TA patients. This data suggests that arterial damage could occur due to previous infection with M. tuberculosis.

The activity of the enzyme methylenetetrahydrofolate reductase (MTHFR) determines homocysteine (Hcy) levels, and polymorphisms in its gene affect the activity of the enzyme. Changes in the enzyme's activity may lead to a higher susceptibility to develop arterial and venous thromboembolic disease. The aim was to analyze the relationship between the C677T and A1298C polymorphisms of MTHFR, Hcy levels, and prothrombotic biomarkers in pulmonary embolism (PE) and acute myocardial ischemia (AMI). Clinical files of patients with thromboembolic diseases having complete data and whose doctor had requested an assay to determine the polymorphisms of the MTHFR gene, Hcy levels, and prothrombotic biomarkers were studied to search for the correlation between mutations of the MTHFR gene and Hcy levels in the different diseases. We included 334 files: 158 were from women and 176 from men (51 [19 SD] years). Sixty-three percent have had thrombosis, 8% AMI, and 31% PE. Patients with thrombosis had elevated frequency of the C677T polymorphism. The CC genotype was higher than the TT genotype ( P = .003) and CT versus the TT ( P = .009). In patients with PE, the CC genotype was higher than the TT genotype ( P = .038). Pulmonary embolism with massive and submassive events had predominant genotypes 677 TT ( P = .003) and the AA 1298 ( P = .017). Elevated Hcy levels in the presence of the T allele in the C677T gene and of the A allele in the A1298C gene are associated with AMI and massive and submassive PE.

The depletion of GSH, in spite of the elevated activity of GR, not only diminished the activity of GSH-depend GST and GPx, but increased LPO, carbonylation and decreased TAC. These changes could promote the structural and functional alterations in the thoracic aorta of MFS patients.

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The in vitro and in vivo data reported here indicate that Ang II upregulates LRP1 receptor expression and LRP1-mediated aggregated LDL uptake in vascular cells.

High-density lipoproteins (HDL) includes a heterogeneous class of lipoproteins grouped into various subclasses that seem to have different antiatherogenic function. Cholesteryl ester transfer protein (CETP) and lecithin cholesterol acyltransferase (LCAT) play an active role in HDL remodeling. This study was designed to define the role of CETP and LCAT activities on HDL-cholesterol (HDL-C) plasma levels and HDL size distribution, as determined by nondenaturating polyacrylamide gradient gel electrophoresis in 47 clinically healthy Mexican individuals without personal and family history of coronary heart disease. Surprisingly, plasma activities of CETP (29+/-4.1% of transfer) and LCAT (4.8+/-2.2% of esterification) did not correlate either with HDL-C plasma levels or with any other lipid parameter, indicating the poor contribution of these proteins to the lipid profile. The CETP activity showed a negative correlation with small HDL3b (r = -0476, P < 0.05), whereas LCAT was positively associated with this HDL subclass (r = 0.466, P < 0.05). The LCAT showed a negative correlation with large HDL2a (r = - 0.674, P < 0.005). Nevertheless, when the LCAT/CETP ratio was calculated, we observed that the higher the ratio, the greater the relative proportion of small HDL3b (r = 0.551, P < 0.05) and HDL3c (r = 0.477, P < 0.05). These results suggest that the balance of LCAT and CETP activities have a great impact in the plasma HDL size distribution.

Background: Takayasu's arteritis (TA) is an idiopathic chronic inflammatory disease that causes occlusion of large arteries, but little is known about whether affected patients are characterized by endothelial dysfunction, different high-density lipoproteins (HDL) subclasses and paraoxonase-1 (PON1) activity. Methods and Results:In the present study, 30 patients with TA, 30 age-and gender-matched volunteers (controls) and 15 patients with essential hypertension were studied. Flow-mediated vasodilation (FMD) and maximal blood flow velocity, assessed in the brachial artery by high-resolution ultrasound, were significantly lower in patients. HDL subclass distribution was determined by polyacrylamide gradient gel electrophoresis. HDL-cholesterol, HDL3b subclass and PON1 activity, assessed spectrophotometrically using phenylacetate as the substrate, were also lower in patients compared with controls. In a multiple regression analysis, the use of prednisone and systolic blood pressure were independent variables that predicted the FMD. Conclusions: A low FMD, abnormal size distribution of HDLs, and low PON1 activity are observed in TA patients. These abnormalities appear independently and constitute a cluster that may contribute to the vascular dysfunction of TA arteritis. (Circ J 2009; 73: 760 -766)

Background Adequate maternal thyroxine (T4) concentrations during the first half of pregnancy are fundamental to the embryo’s or fetus’ neural development. Organophosphate pesticides (OP) can act as thyroid disruptors and genetic polymorphisms for paraoxonase 1 (PON1), an enzyme that detoxifies OP, could be involved in individual’s susceptibility to them. We assessed the association between para-occupational exposure to pesticides, including OP, during pregnancy and maternal hypothyroxinemia, as well as the potential genetic susceptibility conferred by PON1 polymorphisms. Methods We analyzed information from 381 healthy pregnant women (< 17 gestational weeks), who lived in a floricultural region of Mexico where pesticides, including OP, are routinely used. Women who were para-occupationally exposed to pesticides were those whose partner had an occupation involving contact with these products. Thyroid-Stimulating Hormone (TSH) and free T4 concentrations were determined using ELISA, and hypothyroxinemia was defined as free T4 concentrations <0.76 ng/dL. PON1192QR , PON155LM and PON1–108CT polymorphisms were determined through Polymerase Chain Reaction (PCR). The association between para-occupational exposure and genetic polymorphisms and hypothyroxinemia was estimated using logistic regression models. Results One hundred and sixty two women (42.52%) were classified as para-occupationally exposed to pesticides. Hypothyroxinemia prevalence was 54%, and it was not significantly associated with pesticide para-occupational exposure (OR: 1.21 95% CI 0.75–1.94). Independently of para-occupational exposure, the likelihood of hypothyroxinemia was higher among women who were carriers of PON155MM than in those with PON155LL genotype (OR MM vs LL : 3.03; 95%CI 1.62, 5.70). PON1192 RR (OR RR vs QQ : 1.72; 95%CI 0.93, 3.17) and PON1–108TT (OR TT vs CC : 1.60; 95%CI 0.90, 2.70) genotypes were marginally associated with hypothyroxinemia. No significant interaction was observed between pesticides para-occupational exposure and PON1 polymorphisms. Conclusions These results suggest that PON1 polymorphisms could affect thyroid function during pregnancy in women living in areas where pesticides, including OP, are routinely used. Low exposure variability in this population, could be a possible explanation for the lack of association between para-occupational exposure and thyroid function.